Antidepressants were traditionally considered to have delayed onset of action, and clinical opinion often stated that patients may not experience noticeable improvement for 4-6 weeks. Recent studies have shown, however, that antidepressants have more rapid onset of effect, within 1-2 weeks, and that this early response may be associated with later sustained response. Moreover, there is emerging evidence that some medications may have faster onset of therapeutic effect than others. The new antidepressant agomelatine, with its novel pharmacological profile as an agonist at melatonergic (MT(1) and MT(2)) receptors and antagonist at 5-HT(2C) receptors, has in several studies produced earlier symptom improvement than comparator selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors. In particular, beneficial effects on sleep and daytime functioning are noticeable as early as the first week of treatment. These therapeutic benefits may, in part, be related to its regulatory effects on circadian and sleep- wake cycles. Agomelatine therefore combines early symptom relief with a favorable side-effect profile and short-term and long-term antidepressant efficacy. These properties suggest that agomelatine can be considered a first-line treatment for patients with major depression.